ABSTRACT
Background and study aims Conscious sedation is routinely administered for colonoscopy but is associated with risks and inconveniences. We sought to determine whether virtual reality (VR) may be a feasible alternative. Patients and methods Twenty-seven individuals scheduled for screening/surveillance colonoscopy participated. The VR device was activated throughout the colonoscopy, but subjects could opt out and request standard medications. Questionnaires were administered, and variables were assessed on a scale of 1 to 10. Results Cecal intubation was achieved in all cases without adverse events (AEs). Study colonoscopies were completed without pharmacological rescue in 26 of 27 patients (96.3â%) and procedure times were comparable to baseline. Subjects reported minimal pain, high satisfaction, and willingness to use VR for future colonoscopies to avoid narcotics and resume normal activities including driving. Conclusion Replacing pharmacological sedation with VR did not impact colonoscopy completion rates, procedure time, or AEs. Satisfaction was high and only one subject (3.7â%) chose to suspend VR. VR can be an effective alternative for patients undergoing colonoscopy who prefer to avoid narcotics.
ABSTRACT
The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.
Subject(s)
Colonic Neoplasms/microbiology , Colorectal Neoplasms, Hereditary Nonpolyposis/microbiology , Gastrointestinal Microbiome/genetics , Adenoma/microbiology , Adult , Aged , Aged, 80 and over , Colectomy/adverse effects , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Feces/microbiology , Female , Humans , Male , Metagenomics , Middle Aged , Prospective Studies , RNA, Ribosomal, 16S/genetics , Transcriptome , Tumor MicroenvironmentABSTRACT
Background and study aim: Obstruction of biliary self-expandable metal stents (SEMSs) is seen frequently. Radiofrequency ablation (RFA) causes tissue necrosis. This study aimed to assess the efficacy of RFA for management of occluded SEMS. Patients and methods: Patients with biliary malignancy and treated for an occluded SEMS were retrospectively reviewed. The study group comprised patients treated with RFA using an Habib endoprobe inside the SEMS.âThe control group comprised patients treated only with insertion of a plastic stent into an occluded SEMS.âThe end points were; 90-day stent patency rate, time to stent reocclusion, 30-day mortality, and 3â-âand 6-month survival rates. Results: During the 5-year study period 25 patients with an occluded SEMS underwent RFA and 25 patients underwent a plastic stent placement only. Both groups were matched for age and diagnosis. Immediate biliary drainage was restored in all patients. In the RFA group, the stenosis was ablated successfully in 14 patients (56â%); ablation failed in 11 and a plastic stent was then inserted into the SEMS for these. The control group had only placement of a plastic stent across the stenosis. Stent patency rate at 90 days was 56â% and 24â% in the RFA and control groups, respectively (Pâ=â0.04). The mean stent patency time was significantly longer in the RFA group compared to the control group (119.5 vs. 65.3 days, Pâ=â0.03). Conclusion: The application of RFA for occluded SEMS improves stent patency. RFA is an alternative treatment of tissue ingrowth in malignant biliary obstruction.
Subject(s)
Biliary Tract Neoplasms/complications , Catheter Ablation , Cholestasis/surgery , Prosthesis Failure , Self Expandable Metallic Stents/adverse effects , Aged , Cholestasis/etiology , Endoscopy, Digestive System , Female , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Gastrointestinal endoscopy is a remarkably safe set of diagnostic and therapeutic techniques, and yet a small number of significant complications and adverse events are expected. Serious complications may have a material effect on the patient's health and well-being. They need to be anticipated and prevented if possible and managed effectively when identified. When complications occur they need to be discussed frankly with patients and their families. Informed consent, prevention, early detection, reporting, and systems improvement are critical aspects of effective complication management. Optimal complication management may improve patient satisfaction and outcome, as well as preserving the reputation and confidence of the endoscopist, and may minimize litigation.
Subject(s)
Digestive System Diseases/diagnosis , Endoscopy, Gastrointestinal/adverse effects , Postoperative Complications , Early Medical Intervention , Endoscopy, Gastrointestinal/methods , Humans , Informed Consent , Patient Care Management/methods , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Quality ImprovementABSTRACT
Colonoscopy is an invaluable tool for the screening and diagnosis of many colonic diseases. For most colonoscopies, moderate sedation is used during the procedure. However, insufflation of the colon produces a nociceptive stimulus that is usually accompanied by facial grimacing/groaning while under sedation. The objective of this study was to evaluate whether a nociceptive signal elicited by colonic insufflation could be measured from the brain. Seventeen otherwise healthy patients (age 54.8 ± 9.1; 6 female) undergoing routine colonoscopy (ie, no history of significant medical conditions) were monitored using near-infrared spectroscopy (NIRS). Moderate sedation was produced using standard clinical protocols for midazolam and meperidine, titrated to effect. Near-infrared spectroscopy data captured during the procedure was analyzed offline to evaluate the brains' responses to nociceptive stimuli evoked by the insufflation events (defined by physician or observing patients' facial responses). Analysis of NIRS data revealed a specific, reproducible prefrontal cortex activity corresponding to times when patients grimaced. The pattern of the activation is similar to that previously observed during nociceptive stimuli in awake healthy individuals, suggesting that this approach may be used to evaluate brain activity evoked by nociceptive stimuli under sedation, when there is incomplete analgesia. Although some patients report recollection of procedural pain after the procedure, the effects of repeated nociceptive stimuli in surgical patients may contribute to postoperative changes including chronic pain. The results from this study indicate that NIRS may be a suitable technology for continuous nociceptive afferent monitoring in patients undergoing sedation and could have applications under sedation or anesthesia.
Subject(s)
Brain/physiopathology , Colonoscopy , Nociception/physiology , Pain Management , Pain/drug therapy , Spectroscopy, Near-Infrared , Adult , Aged , Analgesics, Opioid/therapeutic use , Brain/drug effects , Colonoscopy/methods , Conscious Sedation/methods , Female , Humans , Hypnotics and Sedatives/therapeutic use , Male , Midazolam/therapeutic use , Middle Aged , Pain/physiopathology , Pain Management/methodsABSTRACT
BACKGROUND: Endoscopic ampullectomy is increasingly performed in patients with familial adenomatous polyposis (FAP)-associated ampullary adenomas. We sought to define the procedure-associated morbidities and long-term outcomes. METHODS: We performed a retrospective chart review of patients with FAP who underwent endoscopic ampullectomy at two tertiary institutions between 1999 and 2010. The severity of duodenal polyposis was classified according to Spigelman's classification. RESULTS: Of 26 FAP patients who underwent endoscopic ampullectomy, 21 arose in the setting of Spigelman's stage II duodenal polyposis. Adverse events associated with endoscopic ampullectomy included acute pancreatitis (19.2%), abdominal pain (7.6%), and bleeding (3.8%). The mean resected adenoma size was 0.99 ± 0.34 cm. Three adenomas (12.0%) contained foci of high-grade dysplasia. Follow-up data were available for 24 patients. The mean follow-up duration was 84.5 ± 36.2 months. Adenoma recurrence was observed in 14 patients (58.3%; 14/24) at a mean of 38.3 months after initial ampullectomy. Adenomas ≥10 mm recurred more frequently than smaller adenomas (76.9 vs. 36.4%; p = 0.002). Positive margins were not associated with higher recurrence rates. No cancers were observed during long-term follow-up. Three patients underwent a Whipple procedure, but none was performed for a recurrent ampullary adenoma. CONCLUSIONS: Endoscopic ampullectomy in FAP can be performed safely. Because ampullary adenomas frequently recur after endoscopic ampullectomy, close surveillance is essential. Smaller tumors are less likely to recur, suggesting a benefit for early recognition of these lesions.
Subject(s)
Adenoma/surgery , Adenomatous Polyposis Coli/surgery , Ampulla of Vater/surgery , Common Bile Duct Neoplasms/surgery , Endoscopy, Digestive System , Neoplasm Recurrence, Local/pathology , Adenoma/pathology , Adenomatous Polyposis Coli/pathology , Adolescent , Adult , Aged , Colectomy/statistics & numerical data , Common Bile Duct Neoplasms/pathology , Duodenal Neoplasms/pathology , Duodenal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Young AdultABSTRACT
Toxic liver injury is a leading cause of liver failure and death because of the organ's inability to regenerate amidst massive cell death, and few therapeutic options exist. The mechanisms coordinating damage protection and repair are poorly understood. Here, we show that S-nitrosothiols regulate liver growth during development and after injury in vivo; in zebrafish, nitric-oxide (NO) enhanced liver formation independently of cGMP-mediated vasoactive effects. After acetaminophen (APAP) exposure, inhibition of the enzymatic regulator S-nitrosoglutathione reductase (GSNOR) minimized toxic liver damage, increased cell proliferation, and improved survival through sustained activation of the cytoprotective Nrf2 pathway. Preclinical studies of APAP injury in GSNOR-deficient mice confirmed conservation of hepatoprotective properties of S-nitrosothiol signaling across vertebrates; a GSNOR-specific inhibitor improved liver histology and acted with the approved therapy N-acetylcysteine to expand the therapeutic time window and improve outcome. These studies demonstrate that GSNOR inhibitors will be beneficial therapeutic candidates for treating liver injury.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Liver/drug effects , Nitric Oxide Donors/pharmacology , S-Nitrosothiols/pharmacology , Acetaminophen/toxicity , Aldehyde Oxidoreductases/metabolism , Animals , Liver/growth & development , Liver/metabolism , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Nitric Oxide/metabolism , Nitric Oxide Donors/therapeutic use , S-Nitrosothiols/therapeutic use , Zebrafish , Zebrafish Proteins/metabolismSubject(s)
Colon , Crohn Disease , Intestinal Mucosa , Intestinal Obstruction , Postoperative Complications , Adolescent , Colon/pathology , Colon/surgery , Crohn Disease/complications , Crohn Disease/pathology , Crohn Disease/surgery , Humans , Intestinal Mucosa/pathology , Intestinal Mucosa/surgery , Intestinal Obstruction/etiology , Intestinal Obstruction/pathology , Intestinal Obstruction/surgery , Male , Postoperative Complications/pathology , Postoperative Complications/surgeryABSTRACT
Developmental signals determine organ morphology and position during embryogenesis. To discover novel modifiers of liver development, we performed a chemical genetic screen in zebrafish and identified retinoic acid as a positive regulator of hepatogenesis. Knockdown of the four RA receptors revealed that all receptors affect liver formation, however specific receptors exert differential effects. Rargb knockdown results in bilateral livers but does not impact organ size, revealing a unique role for Rargb in conferring left-right positional information. Bilateral populations of hepatoblasts are detectable in rargb morphants, indicating Rargb acts during hepatic specification to position the liver, and primitive endoderm is competent to form liver on both sides. Hearts remain at the midline and gut looping is perturbed in rargb morphants, suggesting Rargb affects lateral plate mesoderm migration. Overexpression of Bmp during somitogenesis similarly results in bilateral livers and midline hearts, and inhibition of Bmp signaling rescues the rargb morphant phenotype, indicating Rargb functions upstream of Bmp to regulate organ sidedness. Loss of rargb causes biliary and organ laterality defects as well as asplenia, paralleling symptoms of the human condition right atrial isomerism. Our findings uncover a novel role for RA in regulating organ laterality and provide an animal model of one form of human heterotaxia.
Subject(s)
Gene Expression Regulation, Developmental , Mesoderm/metabolism , Receptors, Retinoic Acid/metabolism , Zebrafish Proteins/metabolism , Zebrafish/embryology , Zebrafish/metabolism , Animals , Animals, Genetically Modified , Body Patterning , Embryo, Nonmammalian/metabolism , Liver/embryology , Liver/metabolism , Models, Animal , Nodal Protein/metabolism , Phenotype , Receptors, Retinoic Acid/genetics , Signal Transduction , Tretinoin/metabolism , Zebrafish/genetics , Zebrafish Proteins/genetics , Retinoic Acid Receptor gammaABSTRACT
Genetic mapping of mutations in model systems has facilitated the identification of genes contributing to fundamental biological processes including human diseases. However, this approach has historically required the prior characterization of informative markers. Here we report a fast and cost-effective method for genetic mapping using next-generation sequencing that combines single nucleotide polymorphism discovery, mutation localization, and potential identification of causal sequence variants. In contrast to prior approaches, we have developed a hidden Markov model to narrowly define the mutation area by inferring recombination breakpoints of chromosomes in the mutant pool. In addition, we created an interactive online software resource to facilitate automated analysis of sequencing data and demonstrate its utility in the zebrafish and mouse models. Our novel methodology and online tools will make next-generation sequencing an easily applicable resource for mutation mapping in all model systems.
Subject(s)
DNA Mutational Analysis/methods , Software , Zebrafish/genetics , Alleles , Animals , Chromosome Mapping/methods , Chromosomes/genetics , Crosses, Genetic , Female , Gene Frequency , Genomics/methods , Homozygote , Male , Markov Chains , Mice , Mice, Inbred C57BL , Mutation , Polymorphism, Single Nucleotide , Recombination, Genetic , Time FactorsSubject(s)
Bile Ducts/physiopathology , Constriction, Pathologic/therapy , Hypercholesterolemia/etiology , Liver Transplantation/adverse effects , Liver Transplantation/methods , Alkaline Phosphatase/metabolism , Biliary Tract Diseases/etiology , Biliary Tract Diseases/therapy , Bilirubin/metabolism , Constriction, Pathologic/etiology , Female , Hepatitis, Autoimmune/therapy , Humans , Hypercholesterolemia/diagnosis , Liver Function Tests , Living Donors , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN: Multicenter randomized trial. SETTING: Four teaching hospitals. PATIENTS: Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS: Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS: Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.
Subject(s)
Biliary Tract Neoplasms/pathology , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis/therapy , Palliative Care , Stents , Aged , Aged, 80 and over , Biliary Tract Neoplasms/complications , Biliary Tract Neoplasms/therapy , Cholestasis/etiology , Cholestasis/pathology , Cohort Studies , Disease-Free Survival , Equipment Design , Female , Humans , Male , Metals , Middle Aged , Recurrence , Treatment OutcomeABSTRACT
Lower gastrointestinal (GI) hemorrhage is a significant cause of morbidity and mortality, particularly in elderly patients. Lower endoscopic evaluation is established as the diagnostic procedure of choice in the setting of acute lower GI hemorrhage.
Subject(s)
Endoscopy, Gastrointestinal/methods , Gastrointestinal Hemorrhage/therapy , Hemostasis, Endoscopic/methods , Lower Gastrointestinal Tract , Angiodysplasia/complications , Colitis/complications , Diverticulum/complications , Emergencies , Gastrointestinal Hemorrhage/etiology , Hemorrhoids/complications , HumansSubject(s)
Amoxicillin-Potassium Clavulanate Combination/adverse effects , Retinal Vasculitis/diagnosis , Vasculitis/pathology , Adult , Biopsy , Colitis, Ulcerative/complications , Colon/pathology , Diagnosis, Differential , Fever/etiology , Humans , Male , Pilonidal Sinus/surgery , Postoperative Complications , Purpura/etiology , Skin/pathology , Thrombophlebitis/etiology , Vasculitis/diagnosis , Vision Disorders/etiologySubject(s)
Cation Exchange Resins/adverse effects , Colon/pathology , Intestinal Perforation/pathology , Polystyrenes/adverse effects , Sorbitol/adverse effects , Abdominal Pain/etiology , Aged , Aortography , Colon/blood supply , Colon/diagnostic imaging , Coronary Artery Disease/complications , Diagnosis, Differential , Humans , Ileus/diagnosis , Iliac Artery/diagnostic imaging , Intermittent Claudication/complications , Intestinal Perforation/chemically induced , Intestinal Perforation/complications , Ischemia/diagnosis , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Necrosis , Thromboembolism/diagnosis , Tomography, X-Ray ComputedABSTRACT
Duodenoscope assisted cholangiopancreatoscopy allows direct visualization of the pancreatic duct and bile duct. There are several circumstances where direct ductal visualization might be helpful in clarifying a diagnosis or providing targeted treatment. Duodenoscope assisted cholangiopancreatoscopy is currently employed for a variety of indications including: indeterminate ductal strictures and filling defects, marginal chronic pancreatitis, treatment of large intraductal stones, localization of intraductal papillary mucinous tumors, and localization and treatment of hemobilia. There have however been no randomized controlled trials evaluating the diagnostic or therapeutic functions of duodenoscope assisted cholangiopancreatoscopy. This article reviews recent descriptive studies that attempt to clarify the clinical role of this technology.
ABSTRACT
BACKGROUND: The aim of this study was to identify predictors of outcome after pancreatic duct stent placement for duct disruption. METHODS: Patients were identified from endoscopy databases. Disruption was defined by extravasation of contrast from the pancreatic duct during endoscopic retrograde pancreatography. Data collected included demographic information, imaging studies, management before and outcome after stent placement. Success was defined as resolution of the disruption clinically, on radiologic imaging, and/or at endoscopic retrograde pancreatography. RESULTS: Forty-three patients (23 women, 20 men; mean age 57 years, [SD] 15.2 years) were studied. The etiology of pancreatic duct disruption was acute pancreatitis in 24, chronic pancreatitis in 9, operative injury in 7, and trauma in 3 patients. In 25 patients there was resolution of the disruption, whereas stent therapy was unsuccessful in 16 and the outcome was indeterminate in 2 patients. On univariate analysis, stent positioned to bridge the disruption (p = 0.04) and longer duration of stent therapy (p = 0.002) were associated with a successful outcome. Female gender (p = 0.05) and acute pancreatitis (p = 0.05) were associated with a lack of success. On multivariate analysis, only the bridging stent position remained correlated to outcome. Complications occurred in 4 patients. CONCLUSIONS: A bridging stent is associated with a successful outcome after pancreatic duct stent placement for duct disruption.